Identification of Proteins from Interstitium of Trapezius Muscle in Women with Chronic Myalgia Using Microdialysis in Combination with Proteomics

Abstract

BackgroundMicrodialysis (MD) of the trapezius muscle has been an attractive technique to investigating small molecules and metabolites in chronic musculoskeletal pain in human. Large biomolecules such as proteins also cross the dialysis membrane of the catheters. In this study we have applied in vivo MD in combination with two dimensional gel electrophoresis (2-DE) and mass spectrometry to identify proteins in the extracellular fluid of the trapezius muscle.Materials and MethodsDialysate from women with chronic trapezius myalgia (TM; n = 37), women with chronic wide spread pain (CWP; n = 18) and healthy controls (CON; n = 22) was collected from the trapezius muscle using a catheter with a cut-off point of 100 kDa. Proteins were separated by two-dimensional gel electrophoresis and visualized by silver staining. Detected proteins were identified by nano liquid chromatography in combination with tandem mass spectrometry.ResultsNinety-seven protein spots were identified from the interstitial fluid of the trapezius muscle; 48 proteins in TM and 30 proteins in CWP had concentrations at least two-fold higher or lower than in CON. The identified proteins pertain to several functional classes, e.g., proteins involved in inflammatory responses. Several of the identified proteins are known to be involved in processes of pain such as: creatine kinase, nerve growth factor, carbonic anhydrase, myoglobin, fatty acid binding protein and actin aortic smooth muscle.ConclusionsIn this study, by using in vivo microdialysis in combination with proteomics a large number of proteins in muscle interstitium have been identified. Several of the identified proteins were at least two-fold higher or lower in chronic pain patients. The applied techniques open up for the possibility of investigating protein changes associated with nociceptive processes of chronic myalgia.

Multivariate Modeling of Proteins Related to Trapezius Myalgia, a Comparative Study of Female Cleaners with or without Pain

“…In agreement with this an increased myogenic activity and increased myonuclear content have been reported when comparing myalgic and healthy muscle [61]. Moreover, a recent proteomic study of the interstitium of chronic trapezius myalgia indicated profound proteomic alterations in myalgia [62]. At the present it is unclear whether these alterations in contractile and structural proteins are primarily linked to nociceptive/inflammatory or metabolic processes or whether they may be secondary consequences of having a muscle in persistent pain e.g., deconditioning, altered activation patterns etc.…”

Clear differences in cerebrospinal fluid proteome between women with chronic widespread pain and healthy women – a multivariate explorative cross-sectional study

“…Although a pattern of proteins clearly discriminating CWP and CON (Table 2) was found, our study cannot determine if these alterations are primarily due to CNS processes or secondary consequences of peripheral factors. In fact, our group reported prominent proteomic alterations in the interstitium of the trapezius muscle and in biopsies of the same muscle in another cohort of CWP patients and controls 112,113. Interestingly, when comparing the results of this study (Table 2) with a recently published similar study from our group on neuropathic pain patients,45 the top protein lists of the two studies partly overlap, TTR and PEDF being significant proteins in both studies.…”

Algogenic substances and metabolic status in work-related Trapezius Myalgia: a multivariate explorative study

“…The regressions of PPT in the groups separately - both analyses of baseline data and all time points (Tables 4 and 5) - indicated that mechanical pain sensitivity in chronic pain conditions are not just consequences of levels of certain biochemical substances since several of the same and significant variables in both regressions had different signs: blood flow, [lactate], [IL-6], and [BKN]. Possible explanations for these results are that nociceptive, hyperalgesic, myogenic, and other processes are activated in TM but not in CON as discussed above [54, 55]. The separate analyses of mechanical pain sensitivity in the two groups of subjects give the opportunity to detect whether a substance is linked to presence of peripheral sensitization in TM.…”